Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by ectopic bone formation.

Objectives: We aimed to investigate the role of developmental endothelial locus-1 (DEL1) in new bone formation using both in in vitro and in vivo models, and to determine the association between DEL1 and spinal progression in AS.

Methods: DEL1 levels were measured in the plasma and facet joint tissues of AS patients. Additionally, DEL1 levels were measured in osteoclast-derived medium and human osteoblast precursor cells were treated with recombinant DEL1 protein and cilengitide trifluoroacetate, an integrin inhibitor for αvβ3. The effects of these treatments on osteoblast differentiation markers were evaluated. A curdlan-injected SKG mouse model was used to mimic the pathogenesis of AS. At three weeks after curdlan injection, recombinant DEL1 protein or cilengitide was administered for three weeks. The ankles of these mice were assessed for thickness. At the end of six weeks, mice were sacrificed, and micro-CT and histological analyses were performed.

Results: DEL1 expression significantly increased during osteoclast differentiation, peaking in terminal stage and correlates with disease progression in AS mice. In AS patients, systemic plasma DEL1 levels were did not different compared to control group, but they positively correlated with structural damage (mSASSS; R=0.3433,p=0.0195). Local DEL1 expression was markedly higher in AS facet joints, specifically localized to TRAP-positive osteoclasts. Functionally, exogenous DEL1 exacerbated pathological bone formation in vivo and directly stimulated human osteoblast differentiation and mineralization via RUNX2 upregulation. These pro-osteogenic effects were effectively neutralized by Cilengitide, an Integrin αVβ3 inhibitor, which attenuated DEL1-induced RUNX2 expression and matrix mineralization.

Conclusions: Our findings establish DEL1 as a key osteoclast-derived coupling factor that drives pathological new bone formation in AS. By signaling through the Integrin αVβ3-RUNX2 axis, DEL1 promotes pathological bone formation and osteoblast differentiation, suggesting that targeting this pathway may offer a novel therapeutic strategy to prevent structural damage in AS patients.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.